Multimode Laser Optoacoustic Tomography System for Breast Cancer Care The broad objective of the proposed project is to overcome the limitations of current breast imaging methods by developing a novel multimode three-dimensional (3D) breast imager that generates 5 different images based on optoacoustic tomography (OAT) and laser ultrasound tomography (UST). The rationale for combining OAT and laser UST into a multimode breast imaging method is clear and compelling, since both, OAT and UST are individually receiving significant attention as promising breast cancer imaging methods. OAT can provide two types of images: (1) image of the total hemoglobin associated with density of tumor angiogenesis and (2) image of blood oxygen saturation. This functional (molecular) information related to breast tissue blood content can help to detect early but aggressively growing breast tumors that are hard to detect with (x-ray) mammography, especially in radiologically dense breasts of younger women. On the other hand, UST can provide high-resolution anatomical images of breast lesions based on three complementary acoustic properties (1) speed-of-sound (SOS), (2) acoustic attenuation, and (3) ultrasound reflectivity. By combining OAT and laser UST we will establish an imaging system that can provide comprehensive co- registered functional and anatomical information without the need for breast compression, ionizing radiation, or contrast agents. Furthermore, using laser generation of ultrasound we will significantly improve performance (sensitivity and resolution) of the ultrasound tomography. Our hypothesis is that coregistration and correlation of 5 different images, the proposed imaging technology will provide ultimate sensitivity and specificity. When clinically validated, the new multimode 3D imaging technology will transform breast cancer care by providing not only a better screening (detection) method, but also will serve as a highly effective tool for differentiation and characterization of breast tumors, a feature critical for diagnostics and monitoring the immediate effects of various anticancer therapies. In this project, we will develop technology (system hardware and software algorithms) and test this multi-modality imager in clinical studies on patients present with small size non- palpable breast tumors suspicious for malignancy. The Specific Aims of the project are: (1) Develop, fabricate and implement an optoacoustic plus laser ultrasonic 3D tomography imager based on rotating arc-shaped array of ultrawide-band ultrasonic transducers, (2) Develop and evaluate robust OAT image reconstruction methods for use with the developed imager, (3) Develop 3D ultrasound and multimode (OAT+UST) image reconstruction methods for use with the developed imager, and (4) experimentally validate the imaging system using breast mimicking phantoms and 96 human subjects. The successful completion of the project will produce conclusive data to motivate a systematic multicenter appropriately statistically powered FDA-guided study to evaluate the effectiveness of the developed system and determine the full range of clinical indications.